J Med Genet: first published as 10.1136/jmg.7.3.200 on 1 September 1970. Downloaded from Journal of Medical Genetics (1970). 7, 200. Tapeto-retinal Degenerations with Varying Clinical Features in Aland Islanders H. FORSIUS* and A. W. ERIKSSONt During the period 1959-1962, we investigated pigmentosa reported in the literature show a great families afflicted with blindness in the Aland variety of clinical features (for references see archipelago, situated in the northern Baltic Sea be- Forsius and Eriksson, 1964a). tween Finland and Sweden. Among the natives of the Aland islands we observed various types of Kokar Pedigree (Families I-V) tapeto-retinal degeneration: Leber's congenital During 1960-1962 we examined almost all the perma- amaurosis, degeneratio retinae pigmentosa juvenilis, nent population of about 420 in the highly isolated island and retinitis punctata albescens. community of Kokar; in addition we examined many In 1969 we again surveyed the occurrence of poor who had emigrated and returned to Kokar on holidays. sight on the Aland islands, and found new cases of The total number of subjects examined was 565. dystrophic changes of the fundus in young subjects. On scanning the detailed and well-preserved church We also observed progression in some of the cases registers going back to the 1650's we found many persons we had on record. Some were with a record of night blindness, poor vision, or blind- patients also ness, often belonging to the same studied by electroretinography (ERG), electro- sibship or closely re- lated in different ways. copyright. oculography(EOG), electronystagmography (ENG), As manifested in the Kokar families, the disease is anomaloscopy, the Farnsworth 100 Hue Test, characterized by night blindness, usually congenital, and fluorescein angiography, etc. relatively early impairment of vision, which may result in The question arose as to whether these clinically blindness at the age of 10-40 years. In the older age- different retinal abiotrophies of autosomal recessive groups, cases resembling atrophia gyrata were observed type could be due to the same mutant gene, causing (Fig. 1). We have interpreted the great diversity of a great diversity of clinical manifestations, depend- clinical forms of tapeto-retinal degeneration as variants of retinitis punctata albescens, and we believe that the ing partly on pleiotropy (polypheny) and partly on http://jmg.bmj.com/ the difference in age of the patients is one of the main progression of tapeto-retinal degeneration. causes of the differences in clinical picture (for details on This hypothesis was corroborated by the genea- pedigree, etc. see Forsius and Eriksson (1964a) and logical data. Many probands showing different Eriksson and Forsius (1964)). kinds of tapeto-retinal degeneration were found to have ancestors in common, particularly in the more Family I distant ascendancy, though some of them were born Agnes J.-R. Female, born in 1920, IV/4* children. in quite different parts of the Aland archipelago. Has always had night blindness. Reading vision lost at (Water excluded, this archipelago comprises 1505 the age of 36. In 1963, visual acuity in both eyes 0-1 on September 29, 2021 by guest. Protected sq. km., water included about 6,000 sq. km., and the (-1-0 D). Fundus degenerated, obvious choroidal distance sclerosis. ERG extinct. Diagnosis: degeneratio tapeto- between some of the inhabited islands is as retinalis of the type gyrata (Fig. 1). much as 100 km.) A brother (Arnold, J.) became blind at the age of Furthermore it seemed unlikely that the small about 38, a sister (Astrid, J.) at the age of 10-12 years. population of Aland (about 21,000 subjects) would The latter shows Turner's syndrome: 45,X/46,XX show so many different recessively inherited mosaicism (de la Chapelle, 1962; Case 15, p. 58). tapeto-retinal diseases, which are all rare, both in Sweden and in Finland. It should be borne in Family H mind that the atypical forms of degeneratio retinae Gunnevi F. Female, born in 1945, I/1 child, birth- weight 2490 g. Hearing somewhat impaired, probably as a result of bilateral * Address: Department of Ophthalmology, University of Oulu, middle ear inflammation at the age Eye Hospital, Uusikatu 50, Oulu, Finland. of 7-8. Has shown a squint since birth. On ophthal- t Address: Folkhalsan Institute of Genetics, Tologatan 12, mological examination for squinting, changes of the Helsinki 10, Finland. * IV/4 etc., means 4 h born of 4 sibs. 200 J Med Genet: first published as 10.1136/jmg.7.3.200 on 1 September 1970. Downloaded from Tapeto-retinal Degenerations with Varying Clinical Features in Aland Islanders 201 copyright. FIG. 1. Family I (Agnes J.-R.) Left eye of 42-year-old woman with hemeralopia, showing degeneration of the fundus resembling atrophia chorioidea gyrata. ERG extinct. fundus were observed. State in 1969: V. o.dx. 1-25 Visual fields normal. Colour vision: secondary dys- (-3-5 D). V. o.sin. 1-2 (-0 5 D). Fundus: pale chromatopsia varying in type. ERG: b-wave normal. papillae, normal blood vessels. Everywhere in the Diagnosis: retinitis punctata albescens. fundus were abundant small pigment spots. Dark A sister (Inga S.) was diagnosed by Dr. M. Zewi as a adaptation (Goldmann-Weekers), normal in both eyes. case of retinitis punctata albescens. Another sister http://jmg.bmj.com/ Diagnosis: atrophia nervi optici, degeneratio retinae (Carola S. born in 1957) had also shown night blindness pseudopigmentosa ? since infancy. State in 1968 (Dr. Zewi): V. o.dx. 0-2 (cyl +3*0 D ax 90°). V. o.sin. 025 (cyl +3-0 D ax Family m 1000). Abundant small light spots in the equatorial Anna L.-L. Female, born 1883, II/5 children. region of the fundus. Diagnosis: retinitis punctata Investigated in 1959 (she died soon afterwards), showed albescens. polar cataract and pronounced choroidal sclerosis and bone cell pigments in the totally destroyed fundus. Family V on September 29, 2021 by guest. Protected Vision 1/oc, no light projection. Diagnosis: final pic- Agnes E.-N. Female, born in 1900. Parents ture of tapeto-retinal degeneration. closely related. A sister (Anna E.), diagnosed by us as a case of retinitis pigmentosa, became blind at the age of Family IV 47 years. V. o.dx. 10 (-1F25 Dcyl -0-25 ax 90°). Yngve S. Male, bom in 1947, III/4 children. Somewhat narrow retinal blood vessels. V. o.sin. 1J0 Examined by us in 1962 and 1967. No definite pro- (-1*75 D). Somewhat narrow blood vessels. Drusen gression. Has always shown poor night vision. Slight papilla. Sector-shaped choroidal sclerosis with bone- subjective impairment of vision during the past few cell like pigments temporally of the fovea, extending to years. V. o.dx. 1-2 (+ 10 Dcyl-3-75 ax 6°). V. o.sin. the periphery. Visual field defect in this area. After 60 0-9 (+ 1-25 Dcyl -3-5 ax 3°). Fundus: papillae some- minutes of dark adaptation the final light threshold of what prominent, pale. Except at the outermost peri- both eyes was about 104 utpL, which is about 1 log unit phery and the central area, abundant small white spots poorer than normal. Subnormal ERG. (The case has in the fundus, and abundant very small pigmented areas been previously described by Elenius, Forsius, and in the retina (Fig. 2). Fovea and blood vessels normal. Eriksson 1961.) Diagnosis: degeneratio retinae et chori- Dark adaptation much impaired (Goldmann-Weekers). oideae o.sin. Drusen papilla o.sin. Glaucoma simplex o.a. J Med Genet: first published as 10.1136/jmg.7.3.200 on 1 September 1970. Downloaded from 2")02 Forsius and Eriksson Carl Johan L. Male, bom in 1948, I/6 children. Just managed reading at elementary school up to the age of 12, after which he visited a school for the blind. No subjective night blindness. State in 1959: V. o.dx. finger counting in front of the eyes (+ 70 D). V. o.sin. hand movements (+6-0 Dcyl +1-0 ax 900). Fundus yellow papillae, narrow blood vessels. Abundant bone- cell like pigments peripherally and round ones centrally. Rapid jerky nystagmus. Diagnosis: amaurosis congenita (Leber). Birgitta L. Female, bom in 1953, V/6 children. Poor sight since birth, continuously impaired. Has always shown night blindness. State in 1969: vision (1959 and 1969) in both eyes finger counting 0 5 m. (+ 6-0 Dcyl + 40 ax 90°). Central visual field lacking. Papilla pale, swollen-'drusen papilla'. Narrow blood vessels. Very heavy bone-cell pigmentation extending to the periphery. Dark adaptation much impaired (105_106 puL Goldmann-Weekers). ENG: ocular nystagmus. Diagnosis: amaurosis congenita (Leber). Bern L. Male, bom in 1956, VI/6 children. Im- pairment of vision was observed before he was 1 year old. Vision problems particularly in the dusk. State in 1963: V. o.dx. finger counting 3 m. (+ 8-0 Dcyl + 2-5 FIG. 2. Family IV (Yngve S.) Male, 20, with retinitis punctata ax 90°). V. o.sin. finger counting 20 cm. (+2-0 Dcyl albescens. Abundant white spots superficially in the retina and + 2-0 ax 90°). Reddish-yellowish papillae, narrow small pigment particles in the deep layers. arteries, normal veins. All over the fundus, but least in the macular region, pigment spots and streaks, some Main Island Pedigree (Families VI-X) the shape of bone cells. Abundant small white or yellow copyright. spots peripherally in the retina. State in 1969: V. o.a. Family VI. According to the parents, the affected hand movements. Fundus: pale atrophic papillae, subjects showed relatively normal vision up to the age narrow blood vessels in the superficial retinal layer. of 2-4 years, when obvious impairment in the form of Fluorescein angiography revealed total atrophy of the 'near-sightedness' set in.